This research program maintains a focus on the regulation of learning and memory by opioid peptides within the amygdala complex and other related limbic system structures. Behavioral experiments are designed to examine functional similarities between opioid peptides that regulate memory processes and those involved in attention. Testing procedures, i.e. overshadowing; conditioned inhibition, will be used to evaluate whether the effects of pretraining and/or posttraining opiate antagonist treatment are sensitive to manipulating the saliency and/or relevance of cues within a task. Although previous independent lines of investigation have implicated opioid peptides in memory and attention, evidence for a common functional substrate of opioid peptides that regulate the allocation of processing and the preservation information may emerge from these investigations. In order to define the CNS components of opioid peptides that contribute to learning and memory, experiments will examine interactions of opioid peptides with ascending norepinephrine (NE) and basal forebrain cholinergic systems. Experiments with a focus on the septal region and upon septo-hippocampal cholinergic function will complement ongoing research aimed at the amygdala central nucleus where opiate/NE interactions have been implicated in memory function. Finally, research is proposed to further investigate in selected limbic structures the identify of opioid peptides that provide a substrate for the effects of opiate manipulations on learning and memory. Brain systems that are the target of our research, i.e. amygdala, septal region, hippocampus, possess multiple distinct opioid peptide systems. Behavioral tasks, previously identified as sensitive to intracranial manipulations of opioid peptide function at these sites, will be used to determine the conditions that regulate activity in these hererogeneous opioid peptide systems. The content of multiple opioid peptides will be monitored by radioimmunoassays within targeted structures in response selected behavioral manipulations. This work provides an initial step toward characterizing the dynamic function of opioid peptide systems that contribute to learning and memory. The neuroanatomical/neurochemical systems examined in this research are central to understanding normal memory function as well as clinical syndromes characterized by a deterioration of memory.